rs1142326

Variant names:

• chr6-32641435-C-A
• rs1142326
• NM_002122.5:c.208C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32641435-C-A
• chr6-32641435-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_002122.5(HLA-DQA1):​c.208C>A​(p.Arg70Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 13)
  • Exomes 𝑓: 0.0034 (393 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 16 publications found

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

HLA-DQA1-AS1 (HGNC:56667): (HLA-DQA1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.255 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	NM_002122.5	MANE Select	c.208C>A	p.Arg70Arg	synonymous	Exon 2 of 5	NP_002113.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	ENST00000343139.11	TSL:6 MANE Select	c.208C>A	p.Arg70Arg	synonymous	Exon 2 of 5	ENSP00000339398.5
	HLA-DQA1	ENST00000374949.2	TSL:6	c.208C>A	p.Arg70Arg	synonymous	Exon 2 of 4	ENSP00000364087.2
	HLA-DQA1	ENST00000395363.5	TSL:6	c.208C>A	p.Arg70Arg	synonymous	Exon 2 of 5	ENSP00000378767.1

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 114 AN: 77196 Hom.: 1 Cov.: 13

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00129

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.000780

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.000690

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00170

Gnomad OTH AF: 0.00211

GnomAD2 exomes AF: 0.0107 AC: 1799 AN: 167538 AF XY: 0.0110

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.00709

Gnomad ASJ exome AF: 0.0127

Gnomad EAS exome AF: 0.00509

Gnomad FIN exome AF: 0.00393

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.00823

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00342 AC: 3154 AN: 923200 Hom.: 393 Cov.: 27 AF XY: 0.00400 AC XY: 1857 AN XY: 464830

African (AFR) AF: 0.00317 AC: 76 AN: 23980

American (AMR) AF: 0.0107 AC: 231 AN: 21682

Ashkenazi Jewish (ASJ) AF: 0.00818 AC: 129 AN: 15762

East Asian (EAS) AF: 0.00174 AC: 46 AN: 26382

South Asian (SAS) AF: 0.00829 AC: 534 AN: 64424

European-Finnish (FIN) AF: 0.00186 AC: 72 AN: 38784

Middle Eastern (MID) AF: 0.00326 AC: 11 AN: 3370

European-Non Finnish (NFE) AF: 0.00279 AC: 1924 AN: 689948

Other (OTH) AF: 0.00337 AC: 131 AN: 38868

GnomAD4 genome AF: 0.00148 AC: 114 AN: 77282 Hom.: 1 Cov.: 13 AF XY: 0.00157 AC XY: 59 AN XY: 37594

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00147 AC: 32 AN: 21842

American (AMR) AF: 0.00129 AC: 8 AN: 6192

Ashkenazi Jewish (ASJ) AF: 0.00118 AC: 2 AN: 1690

East Asian (EAS) AF: 0.000784 AC: 2 AN: 2552

South Asian (SAS) AF: 0.00168 AC: 4 AN: 2384

European-Finnish (FIN) AF: 0.000690 AC: 4 AN: 5798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 104

European-Non Finnish (NFE) AF: 0.00170 AC: 60 AN: 35286

Other (OTH) AF: 0.00206 AC: 2 AN: 970

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0238 Hom.: 319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1142326; hg19: chr6-32609212; COSMIC: COSV58237183; COSMIC: COSV58237183;